Transient global amnesia as a paraneoplastic manifestation of small cell lung cancer

To describe an unusual presentation of paraneoplastic autoimmune encephalitis manifesting as transient global amnesia (TGA).

We report a clinical case of a 59-year-old woman presenting with recurrent episodes of acute anterograde and retrograde amnesia in the context of a new diagnosis of small cell lung cancer. Clinical assessment, neuroimaging, electroencephalography, cerebrospinal fluid analysis, autoimmune and paraneoplastic antibody testing, and oncological investigations were undertaken. Cognitive performance was serially assessed and neurological outcomes were followed longitudinally in parallel with cancer treatment.

The patient fulfilled clinical criteria for TGA with apparent full recovery but rapidly re-presented with persistent and progressive memory impairment. Neuroimaging and EEG were unremarkable, while cerebrospinal fluid showed lymphocytic pleocytosis and positive anti-neuronal immunofluorescence without a defined antibody. Investigation revealed limited-stage small cell lung cancer. Following systemic chemotherapy, radiotherapy, and immune checkpoint inhibitor therapy, the patient demonstrated marked and sustained cognitive improvement, with MMSE improving from 24/30 to 29/30, paralleling tumor response.

This case supports recurrent TGA-like presentations as a rare manifestation of paraneoplastic autoimmune encephalitis. Rapid recurrence or incomplete recovery after TGA should prompt consideration of autoimmune and neoplastic causes. Improvement with cancer-directed and immunomodulatory therapy reinforces a paraneoplastic etiology and suggests immune checkpoint inhibitors may be used effectively in selected cases.